2016
DOI: 10.1097/mph.0000000000000540
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Pharmacokinetics of Chemotherapeutic Drugs in Pediatric Patients With Down Syndrome and Leukemia

Abstract: Children with Down syndrome (DS) have a 10 – 30 fold increased risk of developing acute myeloid leukemia or acute lymphoblastic leukemia. Patients with DS and leukemia are treated with the same chemotherapeutic agents as patients without DS. Treatment regimens for pediatric leukemia comprise multiple cytotoxic drugs including methotrexate, doxorubicin, vincristine, cytarabine, and etoposide. There have been reports of increased toxicity, as well as altered therapeutic outcomes in pediatric patients with DS and… Show more

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Cited by 19 publications
(20 citation statements)
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“…Altered disposition of specific cytotoxic agents may play a role as well. Pediatric patients with DS displayed higher intracellular thioguanine metabolite concentrations when compared with those without DS . Elevated 42‐hour methotrexate plasma concentrations were observed in subjects with DS .…”
Section: Alterations In Drug Disposition and Drug Responsementioning
confidence: 93%
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“…Altered disposition of specific cytotoxic agents may play a role as well. Pediatric patients with DS displayed higher intracellular thioguanine metabolite concentrations when compared with those without DS . Elevated 42‐hour methotrexate plasma concentrations were observed in subjects with DS .…”
Section: Alterations In Drug Disposition and Drug Responsementioning
confidence: 93%
“…Pediatric patients with DS displayed higher intracellular thioguanine metabolite concentrations when compared with those without DS . Elevated 42‐hour methotrexate plasma concentrations were observed in subjects with DS . Most studies that considered the pharmacokinetics of cytotoxic chemotherapeutic agents in patients with DS postulated that altered cellular environments in the DS setting, rather than pharmacokinetics, drive the differential response to chemotherapy agents .…”
Section: Alterations In Drug Disposition and Drug Responsementioning
confidence: 99%
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“…The prognosis is favorable when total resection is possible, but in patients not amenable to the eradication, chemotherapy, and/or radiotherapy are the only available therapeutic options. However, these regimes rarely lead to a control of the disease and the prognosis is generally poor (5). Between 60 and 65% of grade 2 and grade 3 PXAs are BRAF p.V600E mutated (6, 7) and treatment with Vemurafenib, a BRAF inhibitor approved for the treatment of BRAF —mutated metastatic melanoma, demonstrated efficacy in several cases of primary brain tumor, including PXAs (8).…”
Section: Introductionmentioning
confidence: 99%